Prognostic role of molecular forms of B-type natriuretic peptide in acute heart failure

Background: B-type natriuretic peptide (BNP) molecular forms 5–32, 4–32, and 3–32 are known to be present in the circulation of heart failure (HF) patients. This study investigated the prognostic role of circulating BNP molecular forms on risk prediction for patients with acute HF. Methods: BNP molecular forms were measured in plasma using an immunocapture TOF–mass spectrometry (MS) method. Associations of molecular BNP forms with adverse outcome of all-cause mortality (death) and a composite of all-cause mortality and rehospitalization due to HF (death/HF) at 6 months and 1 year were investigated. Results: BNP molecular forms 5–32, 4–32, and 3–32 were detected in 838 out of 904 patient samples. BNP molecular forms were all able to independently predict death and death/HF at 6 months and 1 year. BNP 5–32 was the superior form with strongest predictive qualities for death at 6 months [adjusted hazard ratio (HR) 1.31, P = 0.005] and 1 year (adjusted HR 1.29, P = 0.002) and death/HF at 1 year (adjusted HR 1.18, P = 0.011). BNP 5–32, 4–32, and 3–32 showed decreased survival rates across increasing tertiles of circulating concentrations (P ≤ 0.004). BNP molecular forms showed prognostic ability comparable with conventional BNP measurements across all end points (P = 0.002–0.032 vs P = 0.014–0.039, respectively) and reduced associations with renal dysfunction (blood urea; Spearman correlation rs = 0.187–0.246 vs rs = 0.369, respectively). Conclusions: BNP molecular forms, notably BNP 5–32, showed association with poor prognosis at 6 months and 1 year in patients with acute HF. This is the first study reporting the prognostic ability of molecular BNP forms in HF patients and demonstrated comparable qualities to conventional BNP measurements.